Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
06 November 1981 to 27 November 1981 & 01 December 1981 to 03 December 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study not carried out in accordance with the relevant guidelines, but appears scientifically acceptable and well reported.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
After a range-finding study involving ten rats, five rats/sex were given 50 mg/kg bw and observed for signs of toxicity for 14 days.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:

- Name of test material (as cited in study report): Potassium tetrachloroplatinate (II)
- Substance type: Orange/brown powder
- Physical state: Solid
- Analytical purity: no data
- Lot/batch No.: 031440A
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Tuck & Sons Ltd, Battlesbridge, Essex
- Age at study initiation: no data
- Weight at study initiation: 151-261 g or (in additional study) 218-332 g
- Fasting period before study: 16-20 hours
- Housing: Maximum of 5 rats (of one sex) per polypropylene cage (solid floor, furnished with softwood sawdust)
- Diet (e.g. ad libitum): ad libitum “Rat Diet” from Nottingham University, School of Agriculture, Sutton Bonington, Near Loughborough, Leics, UK.
- Water (e.g. ad libitum):ad libitum, from mains tap
 Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): no data
- Air changes (per hr): 20 (minimum)
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
A single dose was administered by gavage using an all-metal stomach tube.

VEHICLE
- Concentration in vehicle: 100 mg/ml
- Amount of vehicle (if gavage): 0.25, 0.5, 2.0, 5.0 or 20 ml/kg bw (range-finding study); 0.5 ml/kg bw (main study); 2.0 ml/kg bw (additional study)
- Justification for choice of vehicle: no data
- Purity: “B.P.”

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg bw

Doses:
In the range-finding study, male and female rats were administered test substance at doses of 25, 50, 200, 500 or 2000 mg/kg bw (as a suspension in arachis oil). In the main study, male and female rats were administered 50 mg/kg bw. In an additional study, a dose of 200 mg/kg bw was given to rats of both sexes.
No. of animals per sex per dose:
One rat/sex (range-finding study) and 5 rats/sex (main study and additional study)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 5 days (range-finding study); up to 14 days (main study and additional study) they died within 2 days in the additional study (but intention was to observe for 14 .
- Frequency of observations and weighing: a half, one and four hours post-dosing, then daily for up to 14 days (main study and additional study)
- Necropsy of survivors performed: no data
- Other examinations performed: clinical signs

Statistics:
Acute oral median lethal dose (LD50)

Results and discussion

Preliminary study:
In the range-finding study, and in an additional (single dose-level) study, all rats given 200, 500 and 2000 mg/kg bw died within 2 days. In the main study, no deaths were seen at 50 mg/kg bw and below.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 50 - < 200 mg/kg bw
Mortality:
In the range-finding study, and in an additional (single dose-level) study, all rats given 200 mg/kg bw or more died within one or two days. No deaths were seen at the lower dose levels of 50 and 25 mg/kg bw in the range-finding study. In the main study, none of the ten treated rats given 50 mg/kg bw died within 14 days.
Clinical signs:
Subdued activity and hair standing on end were seen in all rats immediately after dosing with 50 mg/kg bw in the main study. No clinical signs were apparent after 24 hours.

In the additional study, further symptoms of laboured breathing followed by collapse, eye closure, tremors and diarrhoea preceded death.
Body weight:
Not reported.
Gross pathology:
Not reported.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of dipotassium tetrachloroplatinate in the rat was shown to be between 50 and 200 mg/kg bw.
Executive summary:

The acute oral toxicity of dipotassium tetrachloroplatinate was assessed in rats. In a range finding study, groups of Sprague-Dawley rats (1/sex/group) were administered the test item at doses of 25, 50, 200, 500 or 2000 mg/kg bw (in arachis oil) by stomach tube. All rats given 200 mg/kg bw or more died within one day, but no deaths were seen within 5 days at the lower dose levels of 50 and 25 mg/kg bw. Therefore, in the main study, five rats/sex were given 50 mg/kg bw (the highest dose causing no deaths in the range-finding study). All of these animals survived the 14-day observation period. The only clinical symptoms reported were reduced activity and hair standing on end, which ceased to be apparent within 24 hours of dosing. In an additional study, 5 rats/sex given 200 mg/kg bw all died within 2 days. As well as the clinical signs already mentioned, laboured breathing, collapse, eye closure, tremors and diarrhoea preceded death.

 

Considering the results of the range-finding investigation, a more appropriate dose for the additional study would have been between 50 and 200 mg/kg bw.

 

The authors conclude that the acute oral median lethal dose (LD50) of dipotassium tetrachloroplatinate is between 50 and 200 mg/kg bw. Based on the results of this study, dipotassium tetrachloroplatinate should be classified for acute oral toxicity (category 3) according to EU CLP criteria (EC 1272/2008).